Cerebral small vessel disease is a common neurological disease, and its incidence is increasing year by year worldwide. In recent years, research on cerebral small vessel disease has gained more and more attention. Our research aims to visualize publications to identify the hotspots and frontiers of cerebral small vessel disease research, and to provide reference and guidance for further research. Publications related to cerebral small vessel disease were searched from the Web of Science Core Collection and screened according to inclusion criteria. CiteSpace 5.8.R3 was used to evaluate and visualize results, including generating web maps and analyzing annual publications, countries, institutions, bibliographic and co-cited references, and keywords; in this article, we use CiteSpace and VOSviewer for the 2012 Cerebral small vessel disease and bibliometric analysis from January 1, 2022 to April 30, 2022. A total of 3037 papers related to cerebral small vessel disease were retrieved, and the number of published papers showed a steady upward trend. Among them, Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration, the most symbolic references in the field of cerebral small vessel disease have been cited a total of 438 times. Stroke is the most active journal (227 articles) and USA publishes up to 800 articles. Harvard Med SchUniv Edinburgh (133 papers) and Charidimou (85 papers) are the institutions and authors who have made the most contributions in this field, respectively. Among the keywords, most of them are related to the pathogenesis of cerebral small vessel disease. After 2018, gut-brain axis and cortex are the keywords with the strongest number of cited outbreaks. There is increasing evidence that cerebral small vessel disease is a research frontier and may remain a research hotspot in the future.

Context: Wenyang Huayu formula (WYHYF) is a prescription useful for treating stroke. Objective: To evaluate the mechanism of WYHYF in the treatment of ischemic stroke. Materials and methods: Network pharmacology analysis was performed to identify the chemical components and potential targets of WYHYF related to cerebral ischemia-reperfusion. The Cytoscape software and STRING database were used to draw a “drug component target disease” and protein interaction network diagram, respectively. Metascape database was used for gene enrichment analysis, and Autodock vina software was used for molecular docking to determine the pathways and targets of WYHYF. Finally, the pathways and targets were verified in vivo in rats. Results: We identified 277 drug targets and 3777 disease targets of WYHYF. Enrichment analysis of the Kyoto Encyclopedia of Genes and Genomes pathways yielded 222 entries. The results of molecular docking showed that the core components and core proteins had a good binding ability. Validation analysis in the animal model indicated that stigmasterol, C-homoerythrin, luteolin, and other components in WYHYF influence the effects of the Toll-like receptor 4(TLR4)/NF-κB signal pathway on IL-6, IL-1β, and tumor necrosis factor-alpha-α and exert neuroprotective effects, relieve reperfusion injury, and inhibit apoptosis and inflammation. Discussion and conclusions: WYHYF affects ischemic stroke through the interactions of multiple components, targets, and pathways. The mechanism may involve the TLR4/NF-κB signal pathway to inhibit apoptosis, reduce inflammation, and promote angiogenesis.

Objective To explore the mechanism of Wenyang Huayu Formula in the treatment of ischemic stroke based on network pharmacology, molecular docking and experimental verification. Methods The chemical components and potential targets in Wenyang Huayu Formula were obtained by network pharmacology, and the targets related to the pathological process of cerebral ischemia-reperfusion were obtained, and the "drug-component-target-disease" was drawn by Cytoscape software,protein interaction network map was drawn based on STRING database.Gene enrichment analysis was using the Metascape database, and the Autodock vina software was using for molecular docking to determine the pathways and targets of Wenyang Huayu Formula, which were verified by vivo experiments in rats. Results 277 drug targets and 3777 disease targets of Wenyang Huayu Formula were retrieved. The core components were Quercetin, kaempferol, luteolin, etc., and the core targets were AKT1, TP53, IL6, CASP3, IL1β, etc.Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis yielded 222 entries, involving Cellular senescence, TNF signaling pathway, Toll-like receptor signaling pathway, etc. Molecular docking results showed that the core component and the core protein had good binding energy. Vivo experiments results shown that: Stigmasterol, C-Homoerythrinan, luteolin and other components in Wenyang Huayu Formula may act on targets such as IL-6, IL-1β and TNF-α through the TLR4/NF-κB signaling pathway, and play roles in neural protection, reduce reperfusion injury, inhibit apoptosis, anti-inflammatory and other effects. Conclusion The mechanism of ischemic stroke by Wenyang Huayu Formula was the result of multi-component, multi-target and multi-channel interaction, and its mean mechanism may inhibit cell apoptosis, reduce inflammation and promote blood vessels through the TLR4/NF-κB signaling pathway.

Background: The standardized treatment of ischemic stroke (IS) with Shuanglu Tongnao Compound Recipe (SLTNCR) combined with Western medicine has improved the life quality and neurological function of patients and achieved a satisfactory clinical effect. However, the underlying mechanisms of SLTNCR in the treatment of IS remain unclear.Methods: A rat model of IS was prepared using Longa's wire bolus method. SLTNCR was administered by gavage with following doses: low dose, 7.16 g•kg −1 ; middle dose, 14.33 g•kg −1 ; high dose, 28.66 g•kg −1 .The expressions of toll-like receptor 4 (TLR4), tumor necrosis factor (TNF-α), interleukin-1β (IL-1β), IL-6, nuclear factor-κB (NF-κB), etc., brain neuron damage, small intestine structure, and the structure of intestinal flora of rats in the high, medium, and low dose SLTNCR groups as well as the Injury + Clostridium butyricum and Injury + Edaravone groups were detected by 16SrRNA gene sequencing, western blot, hematoxylin-eosin (HE) staining, enzyme-linked immunosorbent assay (ELISA), and polymerase chain reaction (PCR).Results: SLTNCR significantly reduced the brain water content, decreased the cerebral infarct size, and improved the neurological deficits, neuronal damage, small bowel tissue damage, and expression of inflammatory factors [B-cell CLL/lymphoma 2 (Bcl-2), BCL2 associated agonist of cell death (Bad), cleavedcaspase-3] in brain tissue. SLTNCR administration significantly inhibited expressions of TLR4, NF-κB, and inhibitor of nuclear factor kappa B (IκB), and decreased phosphorylation levels of NF-κB and IκB in the small intestinal tissues of IS rats. Moreover, SLTNCR also significantly upregulated the expression of intestinal barrier function-related molecules [zona occludens 1 (ZO-1), occludin, claudin-5] and regulated the expression of colonic TLR4, TNF-α, IL-6, and IL-1β. SLTNCR can improve the symptoms of IS rats by improving brain and small intestinal function, particularly by regulating the TLR4/NF-κB signaling pathway, apoptotic proteins, and inflammatory factors in brain tissue. Gut microbiota analysis helped to identify the pharmacological mechanisms underlying the effects of SLTNCR on intestinal bacterial diversity and flora structure in IS rats.Conclusions: SLTNCR can alleviate symptoms of IS and the potential mechanism of its effect is to protect brain tissue by suppressing inflammation. SLTNCR can also alter the structure and diversity of the bacterial community in IS.